Interstitial cystitis (IC) is a chronic bladder disease manifested by severe bladder pain and urinary frequency and urgency. Using criteria established by the NIDDK, the diagnosis can be made by objective visible findings at cystoscopy. However, IC remains a disease of unknown etiology, inconvenient diagnosis, and unclear natural history. Women comprise 90% of IC cases for unknown reasons. Patients report less life satisfaction than those with end stage renal disease. Identification of risk factors is a proven method for providing clues to pathogenesis of a disease, yet a properly designed study of IC with incident cases, appropriate controls, and attention to disease onset date has never boon performed. Herein we propose such a study comprising national samples of incident IC cases and age and gender matched controls with rigorous attention to onset dates of symptoms. By telephone interview and medical record review, we will identify risk factors for IC and reveal non-bladder syndromes associated with IC. In this group of recent onset cases where a convenient diagnostic test would be most useful, we will test the utility of antiproliferative factor, a urinary factor discovered by Susan Keay of our group. We propose then to follow this well-investigated cohort of IC cases to initiate a natural history study of the disease. This project will allow us to test several hypotheses: 1. That certain features that precede onset of IC symptoms, e.g., bacterial cystitis, distinguish IC cases from controls matched for age and gender, and may be risk factors for the disease. 2) That patients with IC have higher prevalences of certain non-bladder syndromes, e.g., irritable bowel syndrome, than do matched controls. 3) That urine APF, HB-EGF, and/or EGF are sensitive and specific diagnostic markers for IC in patients with symptoms of <=12 months. 4) That patients with IC have remissions and that certain clinical features, e.g., bacterial cystitis at disease onset, are prognostic factors for remissions.